The objectives of this project are to 1) use recombinant DNA techniques to express Borrelia burgdorferi specific antigens to improve the serodiagnosis of Lyme disease, 2) determine immunogenic properties of spirochetal components responsible for infection, and 3) determine the role of antigenic variation as an underlying mechanism for persistent spirochetal infection in hosts in spite of significant antibody response to infection. Efforts to improve the serodiagnosis of Lyme disease have been successful through the cloning and expression of a 39 kDa of B. burgdorferi that is specific and highly immunogenic in both experimentally infected animals and humans naturally exposed to the Lyme spirochete. Kits containing this antigen are under current review by the FDA and should be available within the next year. Preliminary studies exploring in vivo antigenic variation in mice have been completed. Adult laboratory mice, Mus musculus, were shown to be suitable experimental animals for this work. Western blot analysis of immune serum from each of 16 persistently infected mice demonstrated that spirochetes used to infect the mice reacted differently when compared with the spirochetes subsequently reisolated from the mice, demonstrating for the first time that changes in antigenic reactivity had occurred in the spirochete populations during persistent infection. We have now infected Ixodes ticks with cloned populations of B. burgdorferi and these ticks will be used to infect subhuman primates to explore these animals as a model for Lyme disease and in vivo antigenic variation.